General procedure for the preparation of 1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid: to a 4-necked, 3L round-bottomed flask were added ethanol (1500 mL), ethyl 3-((4-fluorophenyl)amino)-3-oxopropanoate (139 g, 617 mmol), sodium ethoxide (65.6 g, 925 mmol), and trans-4-methoxy-3 -buten-2-one (103 g, 925 mmol). The reaction mixture was refluxed for 3 hours. Upon completion of the reaction, the solution was cooled to room temperature and subsequently concentrated under reduced pressure to remove ethanol. The residue was diluted with dichloromethane (700 mL) and 1 M hydrochloric acid (1500 mL). The aqueous phase was extracted with dichloromethane (3 x 500 mL). The organic extracts were combined, washed with saturated aqueous sodium chloride (1000 mL), dried over anhydrous sodium sulfate and subsequently concentrated under reduced pressure. The residue was ground with ethyl acetate (150 mL) for 1 hour at room temperature (10-15°C). After filtration and washing with ethyl acetate (50 mL), 1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid was obtained as a yellow solid (85.3 g, 56% yield). Mass spectrum (m/z): 248 (M + H).
